Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer related deaths. The majority of patients present with high-risk disease that is widely metastatic and aggressive. Historically, less than 30% of these patients achieved long-term disease-free survival and the majority of relapses occurred within the first 24 months following treatment. Survival rates have modestly improved with the addition of high-dose chemotherapy and stem cell rescue, radiotherapy, surgery and biologic therapy, yet 50% of patients still succumb to their disease. Current treatment of neuroblastoma also carries significant acute toxicities and those patients that are cured suffer significant long-term treatment-related morbidities. Therefore, children with high-risk neuroblastoma are in need of novel therapeutic strategies that will improve cure rates without adding to acute and long-term toxicities.